1.1.5.3. Biomimetic Chemistry (e.g. Simplified Model of NADH): Inspiration from Biology:

1.1.5.3.1. Introduction
The inspiration from the flow of information from biology into chemistry give rise to a new chemistry based on the principles used by Nature is defined by Ronald Breslow as “biomimetic chemistry”. According to his definition: "In biomimetic chemistry, we take what we have observed in nature and apply its principles to the invention of novel synthetic compounds that can achieve the same goals … As an analogy, we did not simply make larger versions of birds when we invented airplanes, but we did take the idea of the wing from nature, and then used the aerodynamic principles in our own way to build a jumbo jet.”

1.1.5.3.2. Lession from Biological Action of Coenzyme Thiamine Unit:

1.1.5.3.2.1. Biological role of coenzyme thiamine diphosphate: Coenzyme thiamine diphosphate catalyzes the reactions such as that in pyruvate decarboxylase, a process for which very unusual catalysis would be needed.

Mechanistic insights from Chemistry: It was discovered that the unsuspected chemistry associated with thiazolium ring is responsible for such type of catalysis. The proton on carbon 2 of the thiazolium ring can be fairly readily removed to generate a zwitterion that is the catalytic species derived from thiamine diphosphate (Fig. 4). It was shown that this was the species that catalyzed model reactions for the enzymatic process, in what was the likely process by which thiamine diphosphate operated biologically.

Figure 1.4: The thiazolium ion loses a proton at C-2 to form a zwitterion that has a carbene resonance form. This resonance hybrid species is the catalytic form in biochemical reactions catalyzed by thiamine diphosphate.
The stability of this species was explained in terms of a second resonance form, a carbene, and that many other heterocyclic cationic systems could also form a related species.

Application to Chemical World: Carbenes and Metathesis: In the 50 years since that time, many others have used such zwitterion/carbene species to catalyze chemical reactions and also to serve as ligands for metal ions in important catalytic processes. For example, such a species is the preferred ligand in the metathesis catalyst that was part of the work winning Robert Grubbs a recent Nobel Prize in chemistry. Thus, we saw information transfer in both directions. The work by Ronald Breslow with a chemical model system made it clear how a thiazolium salt such as thiamine could catalyze the biological reactions, and indeed, this turned out to be the correct mechanism for the biochemical process. At the same time, the discovery of this hitherto unsuspected species led to unprecedented chemistry and new and useful catalytic reactions.